Aim: To identify DNA methylation markers for triage in a cohort of human papillomavirus-positive (HPV+) women. Methods: The methylation markers were identified and evaluated for the detection of cervical high-grade squamous intraepithelial lesions (HSILs) or cervical cancer (collectively referred to as 'HSIL+') in HPV+ women (n = 692). Results: Combined PAX1/ST6GALNAC5 methylation testing yielded HSIL+ sensitivity of 0.838 and 0.818, with a specificity of 0.827 and 0.810, in the training and test sets, respectively. For cervical cancer, the specificity and sensitivity were 0.969 and 1.000 in the training set and 0.967 and 0.875 in the test set. Moreover, the combined marker methylation test (0.86; 77/90) was more sensitive than the cytology (0.31; 28/90) for HSIL+. Conclusion: The combined PAX1/ST6GALNAC5 marker may have clinical application for detecting HSIL+ in HPV+ women undergoing screening.
Keywords: HPV screening; cervical intraepithelial neoplasia; clinical performance; cytology; diagnostic accuracy; epigenetic; squamous intraepithelial lesion.